Asthma is a chronic inflammatory lung disease that affects an estimated 23 million Americans (16 million adults), 12 million of whom experience at least one asthma attack annually. The symptoms of asthma cause significant economic burden on the healthcare systems ($18B in 2008) as well as dramatic impact on the quality of patients' lives. Asthma is characterized by airway inflammation and edema. Recently, the long recognized increase in airway wall microvessel density and expanded blood volume have been suggested to contribute significantly to lung function. This project combines the recognized expertise of Professor Elizabeth Wagner, PhD (PI) in pulmonary angiogenesis physiology and Professor Gregory M. Lanza, MD PhD (PD/PI), whose nanomedicine-based molecular imaging and therapy is well known, particularly in the context of angiogenesis in cancer and atherosclerosis. The overarching hypotheses of this proposal are to use nanomedicine approach to noninvasively characterize bronchial angiogenesis (new vessel formation), to deliver acute antiangiogenic therapy to reduce airway remodeling and improve pulmonary function, and to maintain the acute benefits of this new treatment with standard-of-care low dose steroids. PUBLIC HEALTH RELEVANCE: Asthma is pathologically characterized by airway structure remodeling resulting from damage to airway epithelium, eosinophil infiltration, smooth muscle hyperplasia, and basement membrane thickening. Increases in the number and size of vessels within the airway wall have long been recognized as an element of asthma remodeling, occurring in mild, moderate, and severe asthmatic lungs of patients young and old. However, recent studies now point to a functional relationship between the severity of chronic asthma and increasing microvessel density, suggesting that microvascular blood volume contributes significantly to airway obstruction. The overarching hypotheses of this proposal are that nanomedicine approach can be used effectively: 1) to noninvasively quantify bronchial angiogenesis, 2) to deliver acute antiangiogenic therapy to reduce airway remodeling and improve pulmonary function, and 3) to maintain the acute benefits of antiangiogenic treatment with low dose steroids. This nanomedicine approach to asthma employs quantitative image stratification and targeted prodrug nanotherapy in conjunction with current standard of care drugs to offer a clinically translatable approach to ameliorate the progression of moderate to severe asthma ultimately to reduce hospitalizations and home health-care costs.